PE20200699A1 - Composiciones sinergicas que comprenden dimiracetam (r) (1) y dimiracetam (s) (2) en una proporcion no racemica - Google Patents

Composiciones sinergicas que comprenden dimiracetam (r) (1) y dimiracetam (s) (2) en una proporcion no racemica

Info

Publication number
PE20200699A1
PE20200699A1 PE2019002444A PE2019002444A PE20200699A1 PE 20200699 A1 PE20200699 A1 PE 20200699A1 PE 2019002444 A PE2019002444 A PE 2019002444A PE 2019002444 A PE2019002444 A PE 2019002444A PE 20200699 A1 PE20200699 A1 PE 20200699A1
Authority
PE
Peru
Prior art keywords
dimiracetam
racemic
proportion
compositions including
pyrrolo
Prior art date
Application number
PE2019002444A
Other languages
English (en)
Inventor
Michael Scherz
Carlo Farina
Original Assignee
Metys Pharmaceuticals AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Metys Pharmaceuticals AG filed Critical Metys Pharmaceuticals AG
Publication of PE20200699A1 publication Critical patent/PE20200699A1/es

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/28—Compounds containing heavy metals
    • A61K31/282—Platinum compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A61K31/708—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Molecular Biology (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Detergent Compositions (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

Referida a una composicion que comprende los enantiomeros de (R)-3,6,7,7a-tetrahidro-1H-pirrolo[1,5-a]imidazol-2,5-diona ((R)-dimiracetam (1)) y (S)-3,6,7,7a-tetrahidro-1H-pirrolo[1,5-a]imidazol-2,5-diona ((S)-dimiracetam (2)) y/o solvatos o co-cristales farmaceuticamente aceptables de los mismos; en donde un exceso enantiomerico (ee) del (R)-dimiracetam (1) es igual o mayor a 33% y menor que o igual a 54%, en donde la proporcion de (R)-dimiracetam (1) con respecto a (S)-dimiracetam (2) es de 2:1 a 3.3:1. Dicha composicion exhibe una mayor potencia farmacologica (efecto sinergico) que sus correspondientes enantiomeros individuales o racemato; siendo util en el tratamiento y/o prevencion de una enfermedad o trastorno seleccionado preferiblemente de neuropatia sensorial periferica, dolor neuropatico periferico, convulsiones, afecciones psiquiatricas, depresion o deterioro cognitivo
PE2019002444A 2017-05-31 2018-05-30 Composiciones sinergicas que comprenden dimiracetam (r) (1) y dimiracetam (s) (2) en una proporcion no racemica PE20200699A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP17173760 2017-05-31
PCT/EP2018/064125 WO2018219977A1 (en) 2017-05-31 2018-05-30 Synergistic compositions comprising (r)-dimiracetam (1) and (s)-dimiracetam (2) in a non-racemic ratio

Publications (1)

Publication Number Publication Date
PE20200699A1 true PE20200699A1 (es) 2020-06-23

Family

ID=59053899

Family Applications (1)

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PE2019002444A PE20200699A1 (es) 2017-05-31 2018-05-30 Composiciones sinergicas que comprenden dimiracetam (r) (1) y dimiracetam (s) (2) en una proporcion no racemica

Country Status (32)

Country Link
US (2) US10738054B2 (es)
EP (2) EP3735971A1 (es)
JP (2) JP6810983B2 (es)
KR (1) KR102269493B1 (es)
CN (1) CN110719779B (es)
AU (1) AU2018276382B2 (es)
BR (1) BR112019025006A2 (es)
CA (1) CA3061274C (es)
CL (1) CL2019003503A1 (es)
CO (1) CO2019013212A2 (es)
CY (1) CY1123386T1 (es)
DK (1) DK3534898T3 (es)
EA (1) EA201992817A1 (es)
EC (1) ECSP19085426A (es)
ES (1) ES2825498T3 (es)
GE (1) GEP20227336B (es)
HR (1) HRP20201608T1 (es)
HU (1) HUE050981T2 (es)
IL (1) IL270833B (es)
JO (1) JOP20190251A1 (es)
LT (1) LT3534898T (es)
MX (1) MX2019013897A (es)
NI (1) NI201900122A (es)
PE (1) PE20200699A1 (es)
PH (1) PH12019502580B1 (es)
PT (1) PT3534898T (es)
RS (1) RS60957B1 (es)
SG (1) SG11201909720SA (es)
SI (1) SI3534898T1 (es)
UA (1) UA125703C2 (es)
WO (1) WO2018219977A1 (es)
ZA (1) ZA201906863B (es)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JOP20190251A1 (ar) * 2017-05-31 2019-10-21 Metys Pharmaceuticals AG تركيبات تآزرية تشتمل على (r)-ديميراسيتام (1) و(s)-ديميراسيتام (2) بنسبة غير راسيمية
MX2021006243A (es) * 2018-12-04 2021-08-11 Metys Pharmaceuticals AG Composiciones sinergicas que comprenden (r)-2-(2-oxopirrolidin-1-i l)butanamida y (s)-2-(2-oxopirrolidin-1-il)butanamida en una proporcion no racemica.

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1233860B (it) 1988-02-08 1992-04-21 Isf Spa Derivati del peridroazacicloalca (1,2-a) imidazolo ad attivita' nootropa
US5200406A (en) 1988-02-08 1993-04-06 I.S.F. Societa Per Azioni Pharmaceutically useful 2,5-dioxo-1H-octahydroimidazo[1,2-A]azepines
GB9123641D0 (en) 1991-11-07 1992-01-02 Isf Spa Process
AU1400100A (en) * 1998-12-02 2000-06-19 Darwin Discovery Limited Therapeutic product and its use
EP1034826A1 (en) 1999-03-05 2000-09-13 Reuter Chemische Apparatebau Co-crystallization process
ITMI20030573A1 (it) 2003-03-24 2004-09-25 Nikem Research Srl Composti ad azione nootropica, loro preparazione,
WO2008073381A2 (en) * 2006-12-11 2008-06-19 University Of Kentucky Research Foundation Synergistic effects of combinations of nornicotine and opioids for the treatment of pain
AU2012201853B2 (en) 2007-04-16 2013-06-27 Neurotune Ag Use of dimiracetam in the treatment of chronic pain
ITMI20070770A1 (it) 2007-04-16 2008-10-17 Brane Discovery S R L Impiego di dimiracetam nel trattamento del dolore cronico
EP2215073A4 (en) 2007-10-31 2011-04-06 Merck Sharp & Dohme SLEEP MODULATION WITH NR2B RECEPTOR ANTAGONISTS
EP2098526B1 (en) 2008-02-22 2014-01-15 Neurotune AG Nitrogen-containing bicyclic compounds active on chronic pain conditions
US9125898B2 (en) 2008-11-14 2015-09-08 Neurotune Ag Acetam derivatives for pain relief
ES2473271T3 (es) 2010-07-26 2014-07-04 Neurotune Ag Proceso de preparación de dimiracetam
WO2012055057A1 (en) 2010-10-29 2012-05-03 Neurotune Ag Therapeutic use of dimiracetam to prevent the hand & foot syndrome caused by sorafenib
WO2015010217A1 (en) * 2013-07-24 2015-01-29 Neurotune Ag Dimiracetam in the treatment of depression
JOP20190251A1 (ar) 2017-05-31 2019-10-21 Metys Pharmaceuticals AG تركيبات تآزرية تشتمل على (r)-ديميراسيتام (1) و(s)-ديميراسيتام (2) بنسبة غير راسيمية

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DK3534898T3 (da) 2020-09-07
PH12019502580A1 (en) 2020-09-28
GEP20227336B (en) 2022-01-10
CY1123386T1 (el) 2021-12-31
ES2825498T3 (es) 2021-05-17
WO2018219977A1 (en) 2018-12-06
IL270833A (en) 2020-01-30
CL2019003503A1 (es) 2020-04-24
ECSP19085426A (es) 2020-05-29
US20200331919A1 (en) 2020-10-22
EP3534898A1 (en) 2019-09-11
RS60957B1 (sr) 2020-11-30
CA3061274A1 (en) 2018-12-06
JP6810983B2 (ja) 2021-01-13
SI3534898T1 (sl) 2020-11-30
KR20200009093A (ko) 2020-01-29
JP2021073171A (ja) 2021-05-13
PT3534898T (pt) 2020-10-06
AU2018276382B2 (en) 2021-03-25
EA201992817A1 (ru) 2020-04-06
CN110719779A (zh) 2020-01-21
SG11201909720SA (en) 2019-11-28
EP3534898B1 (en) 2020-08-05
HUE050981T2 (hu) 2021-01-28
JOP20190251A1 (ar) 2019-10-21
EP3735971A1 (en) 2020-11-11
ZA201906863B (en) 2021-02-24
MX2019013897A (es) 2020-01-20
KR102269493B1 (ko) 2021-06-25
NZ758086A (en) 2020-12-18
JP7157471B2 (ja) 2022-10-20
IL270833B (en) 2021-05-31
BR112019025006A2 (pt) 2020-06-16
CO2019013212A2 (es) 2020-01-17
AU2018276382A1 (en) 2019-10-31
UA125703C2 (uk) 2022-05-18
CN110719779B (zh) 2022-02-01
NI201900122A (es) 2020-07-01
CA3061274C (en) 2023-03-21
LT3534898T (lt) 2020-12-10
PH12019502580B1 (en) 2020-09-28
JP2020521816A (ja) 2020-07-27
US20180346472A1 (en) 2018-12-06
HRP20201608T1 (hr) 2021-01-08
US10738054B2 (en) 2020-08-11

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